April 14, 2005
Rethinking Asthma Treatment
Mild Cases May Not Benefit From Daily Use of Inhalers;
Awaiting Updated Guidelines
By RACHEL ZIMMERMAN
Staff Reporter of THE WALL STREET JOURNAL

People with mild asthma may not have to take inhaled steroids daily,
according to a new study that contradicts the current standard
recommendations of doctors.

Based on prior research, doctors have generally followed National
Institutes of Health guidelines that say mild, persistent asthmatics --
about four million of the 20 million Americans with the disease --
should take inhaled steroids or other anti-inflammatory drugs every day
to ease symptoms, prevent attacks and protect against lung damage.

But a study in today's New England Journal of Medicine showed that
people with this kind of asthma fared just as well as those on daily
medication by taking steroids intermittently, only when their symptoms
flare up. An editorial accompanying the study says it may transform
clinical practice because the results comply "with the philosophy of
achieving and maintaining control of asthma with the least amount of
medication."

The study offers support to the many mild asthmatics who already resist
daily inhaled steroids and simply take medications as needed. Doctors
say only about 30% of patients who are prescribed inhalant steroids
refill their prescriptions. Inhaled steroids taken long term have been
associated with minor growth impairment and in some cases bone loss,
especially in women. (Though these effects are not as serious as those
associated with stronger, oral steroids, such as prednisone, taken for
severe symptoms.)

And the results may eventually curb the nearly $4 billion in sales of
inhaled steroids and other daily anti-inflammatory asthma drugs in the
U.S. The medications used in the study were the inhaled steroid
budesonide, sold as Pulmicort Turbuhaler, and an anti-inflammatory
pill, zafirlukast, branded as Accolate -- both sold by AstraZeneca PLC
of Britain. An NIH panel is scheduled to release updated treatment
guidelines next year, and the agency says it will consider these new
findings.

Until then, drug-industry analysts expect doctors -- especially
risk-adverse primary-care physicians -- to largely stick with the
current guidelines. The study's authors and other physicians also note
that these findings don't apply to patients with moderate to severe
asthma, who should still continue daily preventive treatment. "This is
an evolution of our understanding of this illness," said John
Oppenheimer, an asthma specialist and clinical associate professor of
medicine at the New Jersey Medical School in Newark who was not
involved in the study. "But we have to temper it by saying clearly that
this only applies to patients with mild asthma."

Nevertheless, Homer Boushey, professor of medicine at the University of
California at San Francisco and a co-leader of the study, estimated
that annual medication costs could decrease by as much as $2 billion if
mild asthmatics took inhaled steroids intermittently instead of daily.

Dr. Boushey was on the NIH panel that in 1997 recommended daily
medications for mild, persistent asthma. Previously, only moderate or
severe asthmatics were urged to adhere to the daily regimen. Now, he
says, "I think, maybe, we went a bit too far." The thinking at the time
was that daily inhaled steroid use might prevent long-term
deterioration of lung function. Now, this new clinical trial lends
fodder to the growing argument that that benefit may not exist --
though researchers say larger, long-term studies are needed to confirm
that.

In the yearlong trial, a group of 225 adult asthmatics was divided into
three smaller groups, each of which was directed to dose themselves
daily. One group was given an inhaled steroid, a second received a kind
of anti-inflammatory drug known as an antileukotriene, and the last was
given placebos -- inhalants and pills -- containing no medication. All
three groups were also given extra inhalants and pills containing real
steroidal medicine, and told they could use them as symptoms dictated.

Changes in lung function and the number of severe attacks were almost
the same among all three groups, even though patients in the group
receiving placebos were actually dosing themselves only from time to
time with the extra inhalants and pills. Participants using inhaled
steroids daily did have more symptom-free days and less bronchial
inflammation. But the study's authors said that because these symptoms
were relatively mild, they were of less concern.

The trial was conducted at some of the nation's top asthma centers,
including UCSF, Harvard Medical School and Columbia Presbyterian
Medical Center and funded by the National Heart, Lung and Blood
Institute. Doctors tracked patients' asthma through a series of tests
measuring air-flow obstruction, severity of symptoms, the number of
days lost from work or school, symptom-free days and asthma-related
quality of life.

Asthma is a chronic disease in which the airways to and from the lungs
become irritated and inflamed, causing wheezing, coughing, chest
tightness and trouble breathing. Asthma is considered mild and
persistent when people have symptoms two to six days a week or
nighttime awakening two to three times a month.

Stephen Mally, 41 years old, of Boston, is typical of mild, persistent
asthmatics. He says he goes for weeks without any symptoms. Then, at
certain times of the year, or when he visits a house full of cats, his
asthma flares and he takes albuterol, a nonsteroid medication that
provides quick relief. He has never seen an allergist and when he goes
to his primary-care doctor once a year, he says, "I probably underplay
my symptoms." Why? "I'd like not to have to go on a daily medication,"
said Mr. Mally, who is a hospital fund-raiser.

A spokesman for AstraZeneca said the company doesn't "anticipate any
impact on our business or change in our strategy as a result of this
study."

Pulmicort Turbuhaler's U.S. sales in 2004 were $151 million, the
company said, and about $576 million when combined with sales of
another formulation of the medicine. That's about 31% of the overall
inhaled steroid market. Its biggest competitor, U.K.-based
GlaxoSmithKline PLC's Flovent, captured about 50% of the market with
2004 sales of $460 million, according to analyst reports.

Accolate's 2004 sales in the U.S. were $94 million, the company said,
or a 4.5% share of the antileukotriene market. Its major competitor,
Merck & Co.'s Singulair posted $1.85 billion in U.S. sales in 2004 with
a 96% market share, analysts said.